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ACID BASE BALANCE & BODY FLUIDAni Retno Prijanti
Renal and Body Fluids ModuleJuni 2008
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Continuous Mixing of Body Fluids
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Water Balance and ECFOsmolality
• To remain properly hydrated, water intake• must equal water output• Water intake sources
Ingested fluid (60%) and solid food (30%)
Metabolic water or water of oxidation (10%)
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Water Balance and ECFOsmolality
• Water outputUrine (60%) and feces (4%)Insensible losses (28%), sweat (8%)
• Increases in plasma osmolality trigger thirst and release of antidiuretic hormone (ADH)
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Water Intake and Output
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Regulation of Water Intake
The hypothalamic thirst center is stimulated:
• By a decline in plasma volume of 10%–15%• By increases in plasma osmolality of 1–2%• Via baroreceptor input, angiotensin II, and
other stimuli
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Regulation of Water Intake
Thirst is quenched as soon as we begin todrink water
Feedback signals that inhibit the thirst centersinclude:
Moistening of the mucosa of the mouth andthroatActivation of stomach and intestinal stretchreceptors
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Regulation of Water Intake: ThirstMechanism
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Regulation of Water Output
Obligatory water losses include:Insensible water losses from lungs and skinWater that accompanies undigested food residues in
fecesSensible water loss of 500ml in urine
Kidneys excrete 900-1200 mOsm of solutes to maintain blood homeostasis
Urine solutes must be flushed out of the body in water
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Influence and Regulation of ADH
Water reabsorption in collecting ducts is proportional to ADH release
Low ADH levels produce dilute urine and reduced volume of body fluids
High ADH levels produce concentrated urine
Hypothalamic osmoreceptors trigger or inhibit ADH release
Factors that specifically trigger ADH release include prolonged fever; excessive sweating,vomiting, or diarrhea; severe blood loss; and traumatic burns
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Electrolyte BalanceElectrolytes are salts, acids, and bases, but
electrolyte balance usually refers only to saltbalance
Salts are important for:Neuromuscular excitabilitySecretory activityMembrane permeabilityControlling fluid movements
Salts enter the body by ingestion and are lostvia perspiration, feces, and urine
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Sodium in Fluid and ElectrolyteBalance
Changes in plasma sodium levels affect:Plasma volume, blood pressureICF and interstitial fluid volumes
Renal acid-base control mechanisms arecoupled to sodium ion transport
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Regulation of Sodium Balance:Aldosterone
Sodium reabsorption65% of sodium in filtrate is reabsorbed in the
proximal tubules25% is reclaimed in the DCT
When aldosterone levels are high, all remaining Na+ is actively reabsorbed
Water follows sodium if tubule permeability hasbeen increased with ADH
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Regulation of Sodium Balance:Aldosterone
The renin-angiotensin mechanism triggers therelease of aldosteroneThis is mediated by the juxtaglomerular apparatus, which releases renin in response to:
Sympathetic nervous system stimulationDecreased filtrate osmolalityDecreased stretch (due to decreased bloodpressure)
Renin catalyzes the production of angiotensin II, which prompts aldosterone release
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Regulation of Sodium Balance:Aldosterone
Low aldosterone cause Na excretion and water willfollow it
High aldosterone levels will cause Na absorption.
For the water to be absorbed ADH must also be present
Adrenal cortical cells are also directly stimulated torelease aldosterone by elevated K+ levels in the ECF
Aldosterone brings about its effects (diminishedurine output and increased blood volume) slowly
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What is the acid base balance
• Acid-base balance is defined by the concentration of hydrogen ions.
• In order to achieve homeostasis, there must be a balance between the intake or production of hydrogen ions and the net removal of hydrogen ions from the body.
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An Acid
• Molecules containing hydrogen atoms that can release hydrogen ions in solutions are referred to as an acid.
• An example of an acid is hydrochloric acid (HCL)
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A Base
• A base is an ion that can accept a hydrogen ion.
• An example of a base is is the bicarbonate ion.( HCO3-)
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How is Acid-Base balance measured
• Hydrogen ion concentration is expressed on a logarithm scale using pH units (part/percentage hydrogen).
• 7.0 being neutral• Body systems carefully control pH of the
body within the range of 7.35-7.45
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pH
• A low pH corresponds to a high hydrogen ion concentration
• The term “Acidosis” refers to the addition of excess hydrogen ions and the body has a pH that falls below 7.35
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pH
• A high pH corresponds to a low hydrogen concentration
• The term “Alkalosis” refers to excess removal of hydrogen ions from the body and has a pH that rises above 7.45
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How the Body defends against fluctuations in pH
Three Systems in the body:
1.Buffers in the blood2.Respiration through the lungs3.Excretion by the kidneys
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Buffers in the Blood
• Buffers are substances that neutralize acids or bases
• Bicarbonate which is a base and carbonic acid in the body fluids protect the body against changes in acidity
• These buffer systems serve as a first line of defense against changes in the acid-base balance
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Respiration through the lungs
• Carbon Dioxide which is formed during cellular metabolism forms carbonic acid in the blood decreasing the pH
• When the pH drops respiration rate increases this hyperventilation increases the amount of CO2 exhaled thereby lowering the carbonic acid concentration and restoring homeostasis
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Excretion by the Kidneys
• The kidneys play the primary role in maintaining long term control of Acid-Base balance
• The kidney does this by selecting which ions to retain and which to excrete
• The kidneys adjust the body’s Acid-Base balance
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The Importance of the Body’s Buffering Systems
• Can be quickly realized if one considers the low concentration of hydrogen ions in the body fluids and the relatively large amounts of acids produced by the body each day
• Example: 80 milliequvilalants of hydrogen is either ingested or produced each day by metabolism.
• Whereas the hydrogen ion concentration of the body fluids normally is only about .0004meq/L
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Acid-Base Balance
• Normal pH 7.35 – 7.45
• Alkalosis or alkalemia – arterial blood pH rises above 7.45
• Acidosis or acidemia – arterial pH drops below 7.35 (physiological acidosis)
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Sources of Hydrogen IonsMost hydrogen ions originate from cellular
metabolism
Breakdown of phosphorus-containing proteins releases phosphoric acid into the ECF
Anaerobic respiration of glucose produces lactic acid
Fat metabolism yields organic acids andketone bodies
Transporting carbon dioxide as bicarbonatereleases hydrogen ions
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Hydrogen Ion Regulation
Concentration of hydrogen ions is regulatedsequentially by:
Chemical buffer systems – act within seconds
The respiratory center in the brain stem – acts within 1-3 minutes
Renal mechanisms – require hours to days to effect pH changes
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Chemical Buffer Systems
Strong acids – all their H+ is dissociated completely in water
Weak acids – dissociate partially in water andare efficient at preventing pH changes
Strong bases – dissociate easily in water andquickly tie up H+
Weak bases – accept H+ more slowly (e.g.,HCO3¯ and NH3)
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Strong and Weak Acids
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Chemical Buffer Systems
One or two molecules that act to resist pHchanges when strong acid or base is added
Three major chemical buffer systemsBicarbonate buffer systemPhosphate buffer systemProtein buffer system
Any drifts in pH are resisted by the entirechemical buffering system
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Bicarbonate Buffer System
A mixture of carbonic acid (H2CO3) and its salt,sodium bicarbonate (NaHCO3) (potassium ormagnesium bicarbonates work as well)
If strong acid is added:Hydrogen ions released combine with the
bicarbonate ions and form carbonic acid (aweak acid)
The pH of the solution decreases onlyslightly
HCl + NaHCO3 = H2CO3 + NaCl
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Bicarbonate Buffer System
If strong base is added:It reacts with the carbonic acid to form
sodium bicarbonate (a weak base)The pH of the solution rises only slightlyNaOH + H2CO3 = NaHCO3 + H2O
This system is the only important ECF buffer
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Phosphate Buffer System
Nearly identical to the bicarbonate systemIts components are:
Sodium salts of dihydrogen phosphate(H2PO4¯), a weak acid
Monohydrogen phosphate (HPO42¯), a weak base
HCl + Na2HPO4 = NaH2PO4 + NaCl
NaOH + NaH2PO4 = Na2HPO4 + H2O
This system is an effective buffer in urine andintracellular fluid
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Protein Buffer SystemPlasma and intracellular proteins are the body’s most
plentiful and powerful buffers
Some amino acids of proteins have:Organic acid groups (weak acids) –COOH (carboxyl)
R-COOH RCOO- + H+Groups that act as weak bases –NH2 (amino)
R-NH2 R-NH3
Amphoteric molecules are protein molecules thatcan function as both a weak acid and a weak base
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Physiological Buffer Systems
The respiratory system regulation of acid-base balance is a physiological buffering system
There is a reversible equilibrium between:Dissolved carbon dioxide and waterCarbonic acid and the hydrogen andbicarbonate ions
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3¯
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Physiological Buffer SystemsDuring carbon dioxide unloading, hydrogen ions
are incorporated into water
When hypercapnia or rising plasma H+ occurs:Deeper and more rapid breathing expels morecarbon dioxideHydrogen ion concentration is reduced
Alkalosis causes slower, more shallow breathing, causing H+ to increase
Respiratory system impairment causes acid-baseimbalance (respiratory acidosis or respiratory alkalosis)
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Renal Mechanisms of Acid-Base Balance
Chemical buffers can tie up excess acids orbases, but they cannot eliminate them from thebody
The lungs can eliminate carbonic acid (volatileacid) by eliminating carbon dioxide
Only the kidneys can rid the body of metabolicacids (phosphoric, uric, and lactic acids andketones) and prevent metabolic acidosis
The ultimate acid-base regulatory organs arethe kidneys
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Renal Mechanisms of Acid-Base Balance
The most important renal mechanisms forregulating acid-base balance are:
Conserving (reabsorbing) or generating newbicarbonate ions
Excreting bicarbonate ions
Losing a bicarbonate ion is the same asgaining a hydrogen ion (the blood becomesacidic); reabsorbing a bicarbonate ion is thesame as losing a hydrogen ion (the bloodbecomes alkaline)
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Renal Mechanisms of Acid-Base Balance
Hydrogen ion secretion occurs in the PCT and in the collecting ducts
Hydrogen ions come from the dissociation ofcarbonic acid
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Reabsorption of BicarbonateCarbon dioxide combines with water in tubule cells, forming
carbonic acid
Carbonic acid splits into hydrogen ions and bicarbonate ions
For each hydrogen ion secreted, a sodium ion and a bicarbonate ion are reabsorbed by thePCT cells
Secreted hydrogen ions form carbonic acid;thus, bicarbonate disappears from filtrate at thesame rate that it enters the peritubular capillaryblood
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Reabsorption of Bicarbonate
Carbonic acid formed in filtrate dissociates torelease carbon dioxide and water
• Carbon dioxide then diffuses into tubule cells, where it acts to trigger further hydrogen ionsecretion
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Generating New BicarbonateIons
Two mechanisms carried out collecting ductscells generate new bicarbonate ions
Both involve renal excretion of acid viasecretion and excretion of hydrogen ions orammonium ions (NH4+)
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Hydrogen Ion ExcretionDietary hydrogen ions must be counteracted by
generating new bicarbonate
The excreted hydrogen ions must bind to buffers in the urine (phosphate buffer system)
Collecting duct cells actively secrete hydrogen ions into urine, which is buffered and excreted
Bicarbonate generated is:Moved into the interstitial space via a cotransport systemPassively moved into the peritubular capillary blood
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Hydrogen Ion Excretion
In response to acidosis:
•�Kidneys generatebicarbonate ions and add them to the blood
•�An equal amount of hydrogen ions are added to the urine
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Ammonium Ion Excretion
This method uses ammonium ions producedby the metabolism of glutamine in PCT cells
Each glutamine metabolized produces twoammonium ions and two bicarbonate ions
Bicarbonate moves to the blood and ammonium ions are excreted in urine
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Ammonium ion Excretion
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Bicarbonate Ion Secretion
When the body is in alkalosis, type B intercalated cells of collecting ducts :
Exhibit bicarbonate ion secretionReclaim hydrogen ions and acidify the blood
The mechanism is the opposite of type A intercalated cells and the bicarbonate ion reabsorption process
Even during alkalosis, the nephrons and collecting ducts excrete fewer bicarbonate ions than they conserve
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Respiratory Acidosis and Alkalosis
Result from failure of the respiratory system tobalance pH
PCO2 is the single most important indicator of respiratory inadequacy
PCO2 levelsNormal PCO2 fluctuates between 35 and 45mm HgValues above 45 mm Hg signal respiratory acidosisValues below 35 mm Hg indicate respiratory alkalosis
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Respiratory Acidosis and Alkalosis
Respiratory acidosis is the most common cause of acid-base imbalanceOccurs when a person breathes shallowly,or gas exchange is hampered by diseasessuch as pneumonia, cystic fibrosis, oremphysema
Respiratory alkalosis is a common result ofhyperventilation
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Metabolic Acidosis
All pH imbalances except those caused by abnormal blood carbon dioxide levels
Metabolic acid-base imbalance – bicarbonate ion levels above or below normal (22-26 mEq/L)
Metabolic acidosis is the second most common cause of acid-base imbalance
Typical causes are ingestion of too muchalcohol and excessive loss of bicarbonateionsOther causes include accumulation of lactic acid, shock, ketosis in diabetic crisis, starvation, and kidney failure
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Metabolic Alkalosis
Rising blood pH and bicarbonate levels indicate metabolic alkalosis
Typical causes are:Vomiting of the acid contents of the stomachIntake of excess base (e.g., from antacids)Constipation, in which excessive bicarbonate is reabsorbed
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Respiratory and Renal Compensations
Acid-base imbalance due to inadequacy of aphysiological buffer system is compensated forby the other system
The respiratory system will attempt tocorrect metabolic acid-base imbalances
The kidneys will work to correct imbalancescaused by respiratory disease
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Respiratory Compensation
• Metabolic acidosis has low pH:• �Bicarbonate level is low• �Pco2 is falling below normal to correct
the imbalanceThe rate and depth of breathing areelevated
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Respiratory Compensation
Metabolic alkalosis has high pH:High levels of bicarbonate
Correction is revealed by:Rising PCO2Compensation exhibits slow, shallow breathing, allowing carbon dioxide to
accumulate in the blood
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Renal Compensation
• To correct respiratory acid-base imbalance,renal mechanisms are stepped up
• Respiratory Acidosis has low pHHas high PCO2 (the cause of acidosis)
In respiratory acidosis, the respiratory rateis often depressed and is the immediate
cause of the acidosisHigh bicarbonate levels indicate the kidneys
are retaining bicarbonate to offset theacidosis
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Renal Compensation
• Respiratory Alkalosis has high pH• �Low PCO2 (the cause of the alkalosis)• �Low bicarbonate levels
The kidneys eliminate bicarbonate fromthe body by failing to reclaim it or byactively secreting it
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Developmental Aspects
• Water content of the body is greatest at birth (70-80%) and declines until adulthood, when it is about 58%
• At puberty, sexual differences in body water content arise as males develop greater muscle mass
• Homeostatic mechanisms slow down with age
• Elders may be unresponsive to thirst clues and are at risk of dehydration
• The very young and the very old are the most frequent victims of fluid, acid-base, and electrolyte imbalances